NCT06501378

Cranial Radiotherapy Plus Chemoimmunotherapy in Untreated Driver-mutation Negative NSCLC With Active Brain Metastasis

Cranial Radiotherapy Plus PD-1/PD-L1 Inhibitors and Chemotherapy in Untreated Driver-mutation Negative Non-small Cell Lung Cancer With Active Brain Metastasis (BRILLIANT-1)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, has a significant risk of brain metastasis (BM). Historically, the median overall survival for advanced NSCLC patients with BM was under six months with traditional chemotherapy. However, recent advancements with immune checkpoint inhibitors (ICIs) have shown promise, with some studies reporting improved intracranial objective response rates, progression-free survival, and overall survival when combined with chemotherapy. Despite these improvements, challenges remain, such as treatment resistance, recurrence, and the need for better therapeutic strategies. Local interventions like stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) have been crucial for treating BM, with SRT being particularly effective. The combination of immunotherapy and radiotherapy is emerging as a synergistic approach, with studies suggesting it may enhance local control and survival rates while maintaining safety. Guidelines recommend SRT for patients with limited BMs, and clinical data support the safety and efficacy of combining brain radiotherapy with immunotherapy. A meta-analysis and other studies have shown promising results with this combination, including local control rates and overall survival benefits, with manageable toxicities. However, there is still a need for more prospective clinical trials to verify the safety and efficacy of combining cranial radiotherapy with immunotherapy in NSCLC patients with BM, especially those without driver gene mutations. Therefore, we plan to conduct a phase 2 prospective study, focusing on combining brain radiotherapy with PD-1/PD-L1 inhibitors. Though most of the current studies excluded patients with active BM, we believe that these patients need more attention. In this trial, we focus on patients with active BM and treat them with PD-1/PD-L1 inhibitor, chemotherapy and SRT/WBRT.

Conditions

• NSCLC Stage IV

Interventions

Type	Name	Description
DRUG	PD-1/PD-L1 inhibitor plus chemotherapy	Active brain metastases patients will receive PD-L1/PD-1 inhibitors and chemotherapy.
RADIATION	SRT/WBRT	Active brain metastases (BM) patients will receive stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) according to their BM condition.

Timeline

• Start date: 2024-07-01
• Primary completion: 2025-01-01
• Completion: 2025-07-01
• First posted: 2024-07-15
• Last updated: 2024-08-28

Locations

1 site across 1 country: China